title: CD4+ T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function.
abstract: Evasion of host immune responses is a prerequisite for chronic bacterial diseases; however, the underlying mechanisms are not fully understood. Here, we show that the persistent intracellular pathogen Brucella abortus prevents immune activation of macrophages by inducing CD4(+)CD25(+) T cells to produce the anti-inflammatory cytokine interleukin-10 (IL-10) early during infection. IL-10 receptor (IL-10R) blockage in macrophages resulted in significantly higher NF-kB activation as well as decreased bacterial intracellular survival associated with an inability of B. abortus to escape the late endosome compartment in vitro. Moreover, either a lack of IL-10 production by T cells or a lack of macrophage responsiveness to this cytokine resulted in an increased ability of mice to control B. abortus infection, while inducing elevated production of pro-inflammatory cytokines, which led to severe pathology in liver and spleen of infected mice. Collectively, our results suggest that early IL-10 production by CD25(+)CD4(+) T cells modulates macrophage function and contributes to an initial balance between pro-inflammatory and anti-inflammatory cytokines that is beneficial to the pathogen, thereby promoting enhanced bacterial survival and persistent infection.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Xavier
authors.forename: Maria G
authors.initials: MG
authors.lastname: Winter
authors.forename: Alanna M
authors.initials: AM
authors.lastname: Spees
authors.forename: Kim
authors.initials: K
authors.lastname: Nguyen
authors.forename: Vidya L
authors.initials: VL
authors.lastname: Atluri
authors.forename: Teane M A
authors.initials: TM
authors.lastname: Silva
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Renato L
authors.initials: RL
authors.lastname: Santos
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D050296:Microbial Viability / Q000276:immunology* / Q000528:radiation effects*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D016328:NF-kappa B; D016753:Interleukin-10